Prenatal Intravenous Magnesium at 30-34 Weeks’ Gestation and Neurodevelopmental Outcomes in Offspring
Authors: Caroline A. Crowther, Pat Ashwood, Philippa F. Middleton, Andrew McPhee, Thach Tran, Jane E. Harding, Jane Alsweiler, Ella Baker, Deb Eaglen, Katie Groom, Helga Hauch, Laura Mackay, Marisa J. Pacella, Alisha Preest, Janice Taylor, Katherine Williamson, Anna Tottman, Nicola Austin, Brian A. Darlow, Bronwyn Dixon, Nicola Ellis, Patricia Graham, Joanna Gullam, Dianne Leishman, Michelle M. Van Dyk, Roland Broadbent, Pauline Dawson, Celia Devenish, Janene Douglas, Frances McCaffrey, Robert Carey, Peter Marshall, Scott Morris, Tran Nguyen, Kirsten Gaerty, Oliver Grupp, Geoffrey Boddice, Ann Green, Kassam Mahomed, Laura Turner, Michelle Baldwin, Amanda Dennis, Eleanor Fisher, Karen Gee, Michael Gee, David Strong, Sharin Asadi, Nataliia Burakevych, Rebecca Griffth, Anushika Kendaragama, Olga Ksionda, Khansaa Kurkchi, Claudia Paine, Sarah Philipsen, Jenny Rogers, Debbie Samuel, Rajesh Shah, Nina Slabkevich, Heather Stewart, Alena Vasilenko, Michael Beckman, Elize Bolton, Jacqueline Chaplin, Catherine Cooper, Jane Fox, Peter Gray, Glenda Hawley, Julie Hickey, Joanne Hoey, Elizabeth Hurrion, Luke Jardine, Janet Kan, Lisa Lynn, Teoni McHale, Dianne Poad, Leith Poulsen, Kym Warhurst, Caitlin Bice, Noni Davis, Julanne Duff, Amanda Jones, Elaine A. Kelly, Emma Magrath, Dianne Malcolm, Kerry-Ann O'Connor, Gillian Opie, Anne-Marie Turner, Susan Walker, Amanda Williamson, Heather Woods, David Hou, Michella Kippen, Jen Schroder, Avril J. Thesing, Sarah Wadsworth, Laxmi Camadoo, Christine Dyer, Stephanie Jones, Alka Kothari, Vesna Markovic, Jenny Owens, Meredith Shallcross, Karen Butterley, Caroline Davis, Antonio De Paoli, Serani Dodson, Matthew Holmes, Hanumesha Kenchapla, Tammy Matzolic, Amy McGregor, Sajid Patel, Samja Simic, Vanessa Andrijic, Vikki Biggs, Susan Brandrick, Silvia Goldstein, Anne Lainchbury, Kei Lui, Sarah Lyons, Antonia Shand, Lee Sutton, Lynette Barnes, Jennifer Bowen, Lyndsey Harvey, Claire Jacobs, Jill Milligan, Jonathan Morris, Tanya Nippita, Rachelle Sau-Harvey, Amy Sparks, Anmaree Wegener, Alice Burnett, Kate Callanan, Jeanie Cheong, Cinzia De Luca, Lex Doyle, Jacobus du Plessis, Julianne Duff, Esther Hutchinson, Stefan C. Kane, Elaine Kelly, Louise Kornman, Dianna Maxwell, Marion McDonald, Megan Poth, James C. Arcus, Marie Cruickshank, Bridget Devoy, Melanie J. Fanning, Kylee Henriksen, Fiona Morse, Amber Schiller, Paul A. Tomlinson, Greg Davis, Ana Dosen, Lynne Roberts, Clare Rowe, Julie Creen, Kellee Gee, Tom Hurley, Linda Pallett, Carmel Smitheram, Annette Thompson, Edward Weaver, Lee-anne Lynch, Rosalynn Pszczola, Joanne Said, Julianne Shekleton, Karina Craine, Judy Fergus, Jo Ford, Annette Harris, Megan Kummer, Chris Thurnell, Cherie Boniface, Audra Davis, Corrinne Dickinson, Susan Ireland, Annemarie Lawrence, Katie Mandell, Sheree Menon, David Watson, Michelle Bennett, Rose Elder, Philippa Hayne, Lorna Massov, Helen Miller, Meghan E. Sandler, Valerie Schenk, Natalie Wilkes, Thabani Sibanda, Warren Davis, Natalie Dill, Nelson Espinoza, Ansar Kunjunju, Ian Wright, Chad Anderson, Vincent Ball, Vineesh Bhatia, Rose Burford-Rice, Daniela Gagliardi, Michaela L. Gooding, Shanshan Han, Bevan Headley, Caroline Holst, Amy Keir, Tech Yee Khong, Anuradha Kochar, Yin Yee Lai, Mary Paleologos, Jeffrey Robinson, Kaye Robinson, Michael Stark, Elise Thompson, Miranda Willet, Yu Zhang
Journal: JAMA (2023)

Importance Intravenous magnesium sulfate administered to pregnant individuals before birth at less than 30 weeks’ gestation reduces the risk of death and cerebral palsy in their children. The effects at later gestational ages are unclear. Objective To determine whether administration of magnesium sulfate at 30 to 34 weeks’ gestation reduces death or cerebral palsy at 2 years. Design, Setting, and Participants This randomized clinical trial enrolled pregnant individuals expected to deliver at 30 to 34 weeks’ gestation and was conducted at 24 Australian and New Zealand hospitals between January 2012 and April 2018. Intervention Intravenous magnesium sulfate (4 g) was compared with placebo. Main Outcomes and Measures The primary outcome was death (stillbirth, death of a live-born infant before hospital discharge, or death after hospital discharge before 2 years’ corrected age) or cerebral palsy (loss of motor function and abnormalities of muscle tone and power assessed by a pediatrician) at 2 years’ corrected age. There were 36 secondary outcomes that assessed the health of the pregnant individual, infant, and child. Results Of the 1433 pregnant individuals enrolled (mean age, 30.6 [SD, 6.6] years; 46 [3.2%] self-identified as Aboriginal or Torres Strait Islander, 237 [16.5%] as Asian, 82 [5.7%] as Māori, 61 [4.3%] as Pacific, and 966 [67.4%] as White) and their 1679 infants, 1365 (81%) offspring (691 in the magnesium group and 674 in the placebo group) were included in the primary outcome analysis. Death or cerebral palsy at 2 years’ corrected age was not significantly different between the magnesium and placebo groups (3.3% [23 of 691 children] vs 2.7% [18 of 674 children], respectively; risk difference, 0.61% [95% CI, −1.27% to 2.50%]; adjusted relative risk [RR], 1.19 [95% CI, 0.65 to 2.18]). Components of the primary outcome did not differ between groups. Neonates in the magnesium group were less likely to have respiratory distress syndrome vs the placebo group (34% [294 of 858] vs 41% [334 of 821], respectively; adjusted RR, 0.85 [95% CI, 0.76 to 0.95]) and chronic lung disease (5.6% [48 of 858] vs 8.2% [67 of 821]; adjusted RR, 0.69 [95% CI, 0.48 to 0.99]) during the birth hospitalization. No serious adverse events occurred; however, adverse events were more likely in pregnant individuals who received magnesium vs placebo (77% [531 of 690] vs 20% [136 of 667], respectively; adjusted RR, 3.76 [95% CI, 3.22 to 4.39]). Fewer pregnant individuals in the magnesium group had a cesarean delivery vs the placebo group (56% [406 of 729] vs 61% [427 of 704], respectively; adjusted RR, 0.91 [95% CI, 0.84 to 0.99]), although more in the magnesium group had a major postpartum hemorrhage (3.4% [25 of 729] vs 1.7% [12 of 704] in the placebo group; adjusted RR, 1.98 [95% CI, 1.01 to 3.91]). Conclusions and Relevance Administration of intravenous magnesium sulfate prior to preterm birth at 30 to 34 weeks’ gestation did not improve child survival free of cerebral palsy at 2 years, although the study had limited power to detect small between-group differences. Trial Registration anzctr.org.au Identifier: ACTRN12611000491965